Steroids



United States Patent() STEROIDS Pietro de Ruggieri and Carlo Ferrari, Milan, Italy No Drawing. Application September 29, 1958 Serial No. 763,798

3 Claims. (c1. zoo-239.55

An object of this invention is a method for preparmg compounds represented by the following formula o il J wherein R is a member selected from the group consisting of OH (double bond 5,6) and (double bond 4,5). By this method compounds of high biological activity in the field of progestative and cortical hormones are obtained.

As starting materials compounds represented by the following formula have been selected.

CHs

CN OH m NJ oxy). These tetrahydropyranylethers are oriented in 17::

position and are completely stable towards Gringnards reagents instead of the free 17 hydroxy compounds; therefore, when treated with methyl-magnesiumbromide or iodide, they aiiord, after decomposition of the ZO-ketimines and at the same time of the ethylene-dioxy group, the pregn-S-ene-Zifl,17u-diol-20-one and the 17m hydroxyprogesterone. The followingexamples are given to further illustrate the products and process of the present invention and are not to be construed as limiting.

Example I .Pregn-5 -ene-3/3,1 7u-diol-20-0ne A solution of 1.0 part of 3fi-acetoxy-androst-S-ene-l7 cyano-l7-ol in 4.0 parts of 2,3-dihydropyran was treated at room temperature for 4 hours with 0.05 part of phosphorus oxychloride. The solution was then. diluted with ether, washed with aqueous sodium carbonate followed by water, dried over sodium sulphate and distilled at reduced pressure. The oily residue consisting of 3fiacetoxy androst 5 ene 17,6 cyano 17oz (2' tetrahydropyranyloxy) was submitted directly to subsequent reaction.

This residue was dissolved in 22.5'parts anisol and 49 parts of an ethereal solution of methyl magnesium iodide (from 3 parts of magnesium) were added. The ether was removed and the mixture kept at 90-95 C. for 16 hours. After decomposition with parts of acetic acid and 60 parts of water, the mixture was refluxed for 15 minutes and the solvent was removed by steam distillation. The aqueous suspension was filtered and crystallized from methanol to yield the pregn--5-ene-3fl,l7adiol-20-one, M. P. 265 C., [a] ==36 (diox.) already known.

A solution of 1.0 part of 3-ethylenedioxy-androst-5- ene-l7-cyano l7-ol in 4.0 parts of 2,3dihydropyran was treated at room temperature for 4 hours with 0.05 part of p-toluenesulfonic acid. The solution was then diluted with ether, washed with aqueous sodium carbonate followed by water, dried over sodium sulphate and distilled at reduced pressure. Crystallization from,ether-petroleum ether led to 3-ethylenedioxy-androst-S-ene-17B- cyano-l7a-(2'-tetrahydropyranyloxy), M. P. 160-162 C.

A solution of 1.5 parts of 3-etbylenedioxy-androst-5- ene-17B-cyano17u-(2-tetrahydropyranyl0xy) in 25 parts of anisol was treated with 45 parts of ethereal solution of methyl magnesium bromide (from 3 parts of magnesium). The ether was removed and the mixture was kept at 95 C. for 16 hours. After decomposition with 70 parts of ice-cooled sulfuric acid 2 N, the mixture was refluxed for 15 minutes, the organic layer separated, and the aqueous-phase was extracted with ether.

The combined organic extracts were washed with water and distilled by steam; after filtration of the product, crystallization was accomplished from acetone to give the pregn-4-ene-17a-ol-3,20-dione, M. P. 2l8-220 C., [on] =+104 (acetone) already known.

We claim:

1. A method for the preparation of compounds having the general formula selected from the group consisting of bromide and iodide,

3 a 4 i and finally decomposing with "an acid selected from the References Cited in the file of this patent group consisting of sulfuric acid and acetic acid the 1' resulting ZO-Ketimines and at the same time the ethylene- UNITED STA TES PATEBTS dioxy growl 2,136,401 Strassberger Nov. 15, 1938 2. 35-acetoxy-androst-S-ene-17fl-cyano-17a-(2'-tetrahy- 5 2,326,756 Butenafldt 1943 dropyranyloxy). 4

3. 3-ethylenedioxy-androst-S-ene-l7fl-cyano-17a-(2-tet- OTHER REFERENCES rahydropyranyloxy). Julian et al.: I. A. C. 8., vol. 72, pages 367-70 (1950). 

2. 3B-ACETOXY-ANDROST-5-ENE-17B-CYANO-17A-(2''-TETRAHYDROPYRANYLOXY). 